Folate-conjugated stealth archaeosomes for the targeted delivery of novel antitumoral peptides

Abstract

In this work, novel archaeosomes based on Egg-PC and a mixture of PEGylated archaeal tetraether lipids were investigated as nanocarriers for in vitro delivery of an original anticancer peptide. With the aim to develop site-specific drug targeting, a tetraether equipped with a folate ligand at the PEG₅₀₀₀ terminal end (FA–PEG₅₀₀₀–tetraether) was synthesized in order to bind to folate receptors (over)expressed on the tumor cell surfaces. The original peptide A1 and its inactive analogue A1Yala (17 amino acids) were encapsulated into Egg-PC vesicles incorporating FA–PEG₅₀₀₀–tetraether and/or PEG₂₀₀₀–tetraether lipids in order to evaluate the in vitro anticancer activity of A1-loaded archaeosomes. Results showed a particular behaviour when A1 was encapsulated into the folate-equipped archaeosomes particularly during the first hour of incubation.